1. Field of the Invention
This invention concerns antibodies to particular immunogenic peptides and peptide conjugates and to processes for making the antibodies and using them to assay and purify human fibroblast interferon (HFIF).
2. State of the Art
It is known generally that peptides can be used to produce antibodies which are complexed with proteins in an assay for or purification of the protein: Carraway, "Methods of Radio-immunoassay", Jaffe and Behrman, editors, 2nd Edition, N.Y., 1979, pages 143 to 149. Rudden et al, in J. Biol. Chem., 255, 1000 to 1007 (1980), described the use of anti-serum to a synthetic polypeptide representing the 15 carboxyl-terminal amino acids of the human chorionic gonadotropin (hCG) hormone .beta. subunit for precipitation of hCG-.beta. subunit. In another study, Arnon et al, Proc. Nat. Acad. Sci., USA, 68, 1450 to 1455 (1971), used a polymer conjugate of a synthetic peptide consisting of a slightly modified amino acid sequence of residues 64 to 82 of lysozyme, to produce antibodies to lysozyme in rabbits and goats.
Interferons are protein antiviral agents which can be assayed and purified by reaction with specific antibodies. However, until now it was necessary to employ interferon itself to induce antibody formation. The difficulty of obtaining interferon has caused attendant difficulties in its assay and purification. The following references concern interferon assay and purification:
(1) Anfinsen et al, Proc. Nat. Acad. Sci. USA, 71, 3139 to 3142 (1974), describe partial purification of human leukocyte interferon by affinity chromatography using antibodies;
(2) Paucker et al in "Effects of Interferon On Cells, Viruses and the Immune System", edited by Geraldes, Academic Press, New York, 1975, 639 to 651, describe the purification of mouse interferon by antibody affinity chromatography;
(3) Chudzio, J. Immunol. Methods, 1976, 13(1), 63 to 69 (Chem. Abs., 86, 41609Z (1977)), describes a bioassay employing polyethylene glycol for measuring the level of interferon neutralizing antibodies;
(4) Gresser et al, J. Exp. Med., 144, 1305 to 1315 (1976), describe the use of highly potent sheep anti-mouse interferon serum to demonstrate the importance of interferon in the early response to some viral infections;
(5) Skurkovich et al, J. Immunol. Methods, 1978, 19 (2,3), 119 to 124 (Chem. Abs., 88, 134627k (1978)) studied quantitative determination of human leukocyte interferon by microfluorometric immunoassay with fluorescein isothiocyanate-labeled antibodies;
(6) Paucker, Tex. Rep. Biol. Med., 1977, 35, 23 to 28, reviewed antigenic properties of interferon proteins;
(7) Berg et al, Scand. J. Immunol., 8, 429 to 436 (1978), studied purification of human leukocyte, fibroblast and lymphoblastoid interferons by use of antibodies bound to sepharose columns;
(8) Dalton et al, Infection and Immunity, 19, 570 to 574 (1978), studied production of antibodies to human interferon in mice using highly purified human leukocyte interferon for antibody production; and
(9) Stewart, in "Interferons And Their Actions", Gottlieb, editor, CRC Press, N.Y., 1977, pages 49 to 72, summarizes several methods for purifying and characterizing interferons.
The following references concern interferon itself. Knight et al, in Science, 207, 525 (1980) described a sequence of 13 amino-terminal residues of homogeneous human fibroblast interferon. Houghton et al, Nucl. Acids Res., 8, pages 1913 to 1931 (1980), disclosed the sequence of 47 amino-terminal residues of human fibroblast interferon. Additional references are: Houghton, Nature, 285, 536 (1980); Derynck et al., ibid., 542 to 547 (1980); Taniguchi et al., ibid., 547 to 549 (1980); and Taniguchi et al., Gene, 10, 11 to 15 (1980).
Although it is known generally that peptides and peptide/protein conjugates can produce antibodies, there is nothing to suggest the particular peptide of this invention, or that said peptide will produce antibodies which react with human fibroblast interferon. In fact, there appears to be no teaching in the art concerning production of interferon antibodies by any peptide or protein other than interferon itself.
The subject matter of this invention is related to that of the concurrently filed patent application entitled "Immunogenic Interferon Peptides", said application bearing U.S. Ser. No. 172,467.